Dose-finding Study of Metformin With Chemoradiation in Locally Advanced Head and Neck Squamous Cell Carcinoma

NCT ID: NCT02325401

Last Updated: 2020-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-11
• Study Completion Date: 2020-02-21

Brief Summary

The purpose of this research study is to test the safety of adding metformin to standard of care. The standard of care treatment will be cisplatin once every 3 weeks for 3 treatments and radiation for 7 weeks.

Metformin is a medication that is currently used to treat diabetes. Increasing amounts of metformin will be given to groups of patients already receiving normal treatment for their cancer to see if metformin causes any good effects by killing your cancer or bad effects (side effects).

Detailed Description

Patients were registered by contacting the University of Cincinnati Clinical Trials Office. Patients must be registered and consent obtained prior to initiation of any protocol therapy.

Treatment was administered on an outpatient basis. Adverse events and potential risks for metformin and cisplatin and radiation were reported.

Patients must have screening labs performed within 2 weeks of start of treatment including a complete blood count, liver function tests, metabolic renal panel including magnesium, vitamin B12 level, lactate, and C-peptide. Renal panel must be verified within 24 hours of cisplatin administration. They must fulfill inclusion criteria.

The recommended starting dose of metformin in diabetic patients is 500mg orally twice a day which can be escalated by 500mg increments weekly as tolerated with the maximum recommended daily dose of 2550mg.

Cisplatin was given either before or after the radiation therapy fraction that is given on the same day. If radiation is held for more than 2 days (for any reason), cisplatin may be held as well until radiation resumes.

The prescribed radiotherapy dose was be 70 Gy in 2 Gy once-daily fraction size (total of 35 fractions).

Conditions

Head and Neck Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Metformin with Chemoradiation

Metformin administered orally daily to start one week prior to Cisplatin and Radiation Therapy. Metformin dose is escalating.

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

Escalating doses of 2000mg, 2550 mg and 3000mg. Starting 1 week prior to the initiation of chemoradiation and ending the final day of chemo or radiation.

Cisplatin

Intervention Type: DRUG

Dosed at 100mg/m2 on days 1, 22, and 43

Radiation Therapy

Intervention Type: RADIATION

70 Gy in 2 Gy once daily fractions of 35 fractions

Interventions

Metformin

Escalating doses of 2000mg, 2550 mg and 3000mg. Starting 1 week prior to the initiation of chemoradiation and ending the final day of chemo or radiation.

Intervention Type: DRUG

Cisplatin

Dosed at 100mg/m2 on days 1, 22, and 43

Intervention Type: DRUG

Radiation Therapy

70 Gy in 2 Gy once daily fractions of 35 fractions

Intervention Type: RADIATION

Other Intervention Names

Fortamet; Glucophage; Glucophage XR; Glumetza; Riomet; Platinol; Platinol-AQ

Eligibility Criteria

Inclusion Criteria

• Locally advanced squamous cell cancer of the head and neck, stage III or IV disease (T1-2, N2a-3 or T3-4).
• Measurable disease
• No prior chemotherapy or radiation for head and neck squamous cell cancer
• Life expectancy of greater than 3 months.
• Adequate labs

Exclusion Criteria

• Known metastatic disease.
• Nasopharyngeal carcinoma
• History of allergic reactions attributed to metformin or other agents used in study.
• Known diagnosis of diabetes requiring insulin for control.
• Administration of metformin within last 4 weeks.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Trisha Wise-Draper

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Trisha Wise-Draper, MD

Role: PRINCIPAL_INVESTIGATOR

University of Cincinnati

Locations

University of Cincinnati Cancer Institute

Cincinnati, Ohio, United States

Countries

United States

References

Crist M, Yaniv B, Palackdharry S, Lehn MA, Medvedovic M, Stone T, Gulati S, Karivedu V, Borchers M, Fuhrman B, Crago A, Curry J, Martinez-Outschoorn U, Takiar V, Wise-Draper TM. Metformin increases natural killer cell functions in head and neck squamous cell carcinoma through CXCL1 inhibition. J Immunother Cancer. 2022 Nov;10(11):e005632. doi: 10.1136/jitc-2022-005632.

Reference Type: DERIVED

PMID: 36328378 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

UCCI-HN-14-01

Identifier Type: -

Identifier Source: org_study_id